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Research article

Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study

Methods

We evaluated 3,394 patients who presented to National Comprehensive Cancer Network
(NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007.
Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive
(HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression
were used to compare groups.

Results

Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of
total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total)
to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less
likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53,
95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to
2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage
and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable
OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).

As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had
significantly increased hazard of early, but not late, death (hazard ratio of death
zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19
to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI:
0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of
diagnosis).

Conclusions

Presenting features, patterns of recurrence and survival of HER2-positive breast cancer
differed by HR status. These differences should be further explored and integrated
in the design of clinical trials.